Neurocardiac Predictors of Treatment Response to rTMS in Depression (NCP)

Neuro-cardiac Predictors of Treatment Response to rTMS in Depression: A Mechanistic Study Using Interleaved TMS-fMRI

Heartbeat is controlled by the brain and is regular but flexible to change in response to environmental and internal stimuli. This feature is known as heart rate variability (HRV). Major depressive disorder (MDD) has been associated with diminished HRV and this is a reflection of abnormal brain function caused by MDD. Repetitive transcranial magnetic stimulation (rTMS) is a treatment that stimulates specific areas of the brain. The goal of this study is to test the hypothesis that rTMS induces changes in connectivity between the area of the brain stimulated with rTMS and deeper areas in the brain associated to heart rate regulation. 110 patients with TRD will be recruited and will undergo a concurrent TMS-fMRI session before receiving a course of iTBS to the L-DLPFC for 30 sessions at 120% rMT.

Study Overview

• Status: Not yet recruiting
• Conditions: Depression; Treatment Resistant Depression
• Intervention / Treatment: Device: Repetitive Transcranial Magnetic Stimulation

• Study Type: Interventional
• Enrollment (Anticipated): 110
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Quincy Beck, B.Sc.; Phone Number: 604-822-7308; Email: quincy.beck@ubc.ca
• Study Contact Backup: Name: Fidel Vila-Rodriguez, M.D., Ph.D.; Phone Number: 604-827-1361; Email: ninet.lab@ubc.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 2A1
      • Non-Invasive Neurostimulation Therapies (NINET) Laboratory, UBC Department of Psychiatry
      • Principal Investigator: Fidel Vila-Rodriguez, M.D., Ph.D.
      • Contact: Quincy Beck, B.Sc.; Phone Number: 604-822-7308; Email: quincy.beck@ubc.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients will be included if they:

1. are female or male;
2. are outpatients;
3. are voluntary and competent to consent to treatment;
4. have a DSM 5 diagnosis of MDD, single or recurrent confirmed by Mini-International Neuropsychiatric Interview (MINI) version 6.0;
5. are between the ages of 18 and 65 years;
6. have failed to achieve a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score of > 3 in the current episode OR have been unable to tolerate at least two separate trials of antidepressants at less than the minimum adequate dose and/or duration (ATHF 1 or 2);
7. A score ≥ 18 on the Hamilton Depression Rating Scale (HDRS-17 item);
8. Have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening;
9. Able to adhere to the treatment schedule;
10. pass the TMS and MRI adult safety screening questionnaires.

Exclusion Criteria:

Patients are excluded if they:

1. have a history of substance use within the last 3 months;
2. have a concomitant major unstable medical illness;
3. have active suicidal intent;
4. are pregnant;
5. have a lifetime (MINI) diagnosis of any psychotic or bipolar disorder;
6. have a MINI anxiety disorder or personality disorder assessed by a study investigator to be primary and causing greater impairment than MDD;
7. have ever failed a course of ECT;
8. have previously received rTMS;
9. have any significant neurological disorder, any history of seizure (except those therapeutically induced by ECT), significant head trauma with loss of consciousness for > 5 min;
10. have any intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed;
11. if participating in psychotherapy, must have been in stable treatment for at least 3 months prior to study entry, with no anticipated change in the frequency of therapeutic sessions, or focus of therapeutic sessions over the duration of the study;
12. have a clinically significant laboratory abnormality, in the opinion of the one of the principal investigators;
13. are currently taking lorazepam greater than 2 mg daily (or equivalent) or any dose of an anticonvulsant, due to the potential to limit rTMS efficacy;
14. have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview);
15. have failed more than three adequate trials (ATHF > 3) of medication in the current episode.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active iTBS; Active intermittent theta-burst stimulation (iTBS) rTMS session on the left dorsolateral prefrontal cortex (L-DLPFC)	Device: Repetitive Transcranial Magnetic Stimulation; This study utilizes intermittent theta burst stimulation (iTBS) to the left DLPFC.; Other Names: rTMS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Depressive Symptoms using HDRS-17 Scale at Week 10	The 17-item Hamilton Depression Rating Scale (HRSD-17) will be used as the primary outcome measure as well as the tool to establish severity cut off for eligibility (Hamilton, 1960). The scoring ranges from 0-52, with higher scores indicating more severe depression symptoms.	Baseline and Week 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Anxiety Symptoms using HAM-A Scale at Week 10	The 14-item Hamilton Anxiety Rating Scale (HAM-A) will be used as a secondary outcome measure in this study. The scoring of this assessment ranges from 0-56, with higher scores indicating more severe anxiety symptoms.	Baseline and Week 10
Change from Baseline in Depressive Symptoms using QIDS-16 Scale at Week 10	The self-rated 16-item Quick Inventory of Depressive Symptoms (QIDS-16) will be used as a secondary outcome measure in this study. The scoring of this assessment ranges from 0-27, with higher scores indicating more severe depression symptoms.	Baseline and Week 10

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Fidel Vila-Rodriguez, M.D., Ph.D., Department of Psychiatry, UBC

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2022
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: November 17, 2021
• First Submitted That Met QC Criteria: November 17, 2021
• First Posted (Actual): December 1, 2021

Study Record Updates

• Last Update Posted (Actual): February 2, 2022
• Last Update Submitted That Met QC Criteria: January 18, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Heart Rate Variability; fMRI; rTMS; Repetitive Transcranial Magnetic Stimulation; Neurostimulation
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: H19-00648

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No